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Local anesthetic systemic toxicity

Authors
Lisa Warren, MD
Aimee Pak, MD
Section Editor
Robert Maniker, MD
Deputy Editor
Marianna Crowley, MD

INTRODUCTION

Local anesthetics (LAs) are administered in practice by many clinicians, including anesthesiologists, surgeons, emergency room providers, dentists, and others. Despite the widespread use of LAs, awareness of local anesthetic systemic toxicity (LAST) and knowledge of its management are lacking [1,2].

Local anesthetics are often incorrectly thought to be without side effects or toxicity. LAST is always a potential complication, and may occur with all LAs, and any route of administration. LAST primarily affects the central nervous system and cardiovascular system, and may be fatal.

This topic will discuss the pathologic pharmacology, mechanisms, and clinical presentation of toxicity, predisposing factors, and prevention and management of LAST. Lipid rescue therapy will also be discussed.

INCIDENCE OF LAST

The reported incidence of major local anesthetic systemic toxicity (LAST) events (ie, seizures or cardiac arrest) associated with regional anesthesia is very low. Major LAST events have decreased markedly since the early 1980s, likely related to increased awareness and routine incorporation of preventive measures into clinical practice [3,4]. (See 'Prevention of LAST' below.)

Data regarding the incidence of LAST come from registry studies and retrospective reviews of large numbers of regional anesthetics, based on very small numbers of events.

                           
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Literature review current through: Sep 2017. | This topic last updated: Sep 11, 2017.
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References
Top
  1. Collins J. Awareness of local anaesthetic toxicity issues among hospital staff. Anaesthesia 2010; 65:960.
  2. Sagir A, Goyal R. An assessment of the awareness of local anesthetic systemic toxicity among multi-specialty postgraduate residents. J Anesth 2015; 29:299.
  3. Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med 2002; 27:556.
  4. Weinberg G, Barron G. Local Anesthetic Systemic Toxicity (LAST): Not Gone, Hopefully Not Forgotten. Reg Anesth Pain Med 2016; 41:1.
  5. Liu SS, Ortolan S, Sandoval MV, et al. Cardiac Arrest and Seizures Caused by Local Anesthetic Systemic Toxicity After Peripheral Nerve Blocks: Should We Still Fear the Reaper? Reg Anesth Pain Med 2016; 41:5.
  6. Barrington MJ, Kluger R. Ultrasound guidance reduces the risk of local anesthetic systemic toxicity following peripheral nerve blockade. Reg Anesth Pain Med 2013; 38:289.
  7. Auroy Y, Benhamou D, Bargues L, et al. Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service. Anesthesiology 2002; 97:1274.
  8. Sites BD, Taenzer AH, Herrick MD, et al. Incidence of local anesthetic systemic toxicity and postoperative neurologic symptoms associated with 12,668 ultrasound-guided nerve blocks: an analysis from a prospective clinical registry. Reg Anesth Pain Med 2012; 37:478.
  9. Heinonen JA, Litonius E, Pitkänen M, Rosenberg PH. Incidence of severe local anaesthetic toxicity and adoption of lipid rescue in Finnish anaesthesia departments in 2011-2013. Acta Anaesthesiol Scand 2015; 59:1032.
  10. Ecoffey C, Oger E, Marchand-Maillet F, et al. Complications associated with 27 031 ultrasound-guided axillary brachial plexus blocks: a web-based survey of 36 French centres. Eur J Anaesthesiol 2014; 31:606.
  11. Orebaugh SL, Kentor ML, Williams BA. Adverse outcomes associated with nerve stimulator-guided and ultrasound-guided peripheral nerve blocks by supervised trainees: update of a single-site database. Reg Anesth Pain Med 2012; 37:577.
  12. Heavner JE. Local anesthetics. Curr Opin Anaesthesiol 2007; 20:336.
  13. Lirk P, Picardi S, Hollmann MW. Local anaesthetics: 10 essentials. Eur J Anaesthesiol 2014; 31:575.
  14. Catterall WA. Voltage-gated sodium channels at 60: structure, function and pathophysiology. J Physiol 2012; 590:2577.
  15. El-Boghdadly K, Chin KJ. Local anesthetic systemic toxicity: Continuing Professional Development. Can J Anaesth 2016; 63:330.
  16. Scholz A. Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels. Br J Anaesth 2002; 89:52.
  17. Meuth SG, Budde T, Kanyshkova T, et al. Contribution of TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 channels to the control of activity modes in thalamocortical neurons. J Neurosci 2003; 23:6460.
  18. Block A, Covino BG. Effect of local anesthetic agents on cardiac conduction and contractility. Regional Anesthesia 1981; 6:55.
  19. Bardsley H, Gristwood R, Baker H, et al. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998; 46:245.
  20. Scott DB, Lee A, Fagan D, et al. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69:563.
  21. Knudsen K, Beckman Suurküla M, Blomberg S, et al. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth 1997; 78:507.
  22. Groban L. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med 2003; 28:3.
  23. Wolfe JW, Butterworth JF. Local anesthetic systemic toxicity: update on mechanisms and treatment. Curr Opin Anaesthesiol 2011; 24:561.
  24. Hernandez MA, Boretsky K. Chloroprocaine: local anesthetic systemic toxicity in a 9-month infant with paravertebral catheter. Paediatr Anaesth 2016; 26:665.
  25. Cladis FP, Litman RS. Transient cardiovascular toxicity with unintentional intravascular injection of 3% 2-chloroprocaine in a 2-month-old infant. Anesthesiology 2004; 100:181.
  26. Marsch SC, Sluga M, Studer W, et al. 0.5% versus 1.0% 2-chloroprocaine for intravenous regional anesthesia: a prospective, randomized, double-blind trial. Anesth Analg 2004; 98:1789.
  27. Kuhnert BR, Philipson EH, Pimental R, Kuhnert PM. A prolonged chloroprocaine epidural block in a postpartum patient with abnormal pseudocholinesterase. Anesthesiology 1982; 56:477.
  28. Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med 2010; 35:181.
  29. Mahli A, Coskun D, Akcali DT. Aetiology of convulsions due to stellate ganglion block: a review and report of two cases. Eur J Anaesthesiol 2002; 19:376.
  30. Fujiwara S, Komasawa N, Kido H, Minami T. A rare case of accidental arterial local anesthetic injection under ultrasound-guided stellate ganglion block. J Clin Anesth 2016; 29:3.
  31. Vasques F, Behr AU, Weinberg G, et al. A Review of Local Anesthetic Systemic Toxicity Cases Since Publication of the American Society of Regional Anesthesia Recommendations: To Whom It May Concern. Reg Anesth Pain Med 2015; 40:698.
  32. Doumiri M, Moussaoui A, Maazouzi W. [Cardiac arrest after gargling and oral ingestion of 5% lidocaine]. Can J Anaesth 2008; 55:882.
  33. Parish RC, Moore RT, Gotz VP. Seizures following oral lidocaine for esophageal anesthesia. Drug Intell Clin Pharm 1985; 19:199.
  34. Hess GP, Walson PD. Seizures secondary to oral viscous lidocaine. Ann Emerg Med 1988; 17:725.
  35. Dayan PS, Litovitz TL, Crouch BI, et al. Fatal accidental dibucaine poisoning in children. Ann Emerg Med 1996; 28:442.
  36. Ameer B, Burlingame MB, Harman EM. Rapid mucosal absorption of topical lidocaine during bronchoscopy in the presence of oral candidiasis. Chest 1989; 96:1438.
  37. Labedzki L, Ochs HR, Abernethy DR, Greenblatt DJ. Potentially toxic serum lidocaine concentrations following spray anesthesia for bronchoscopy. Klin Wochenschr 1983; 61:379.
  38. Nath MP, Baruah R, Choudhury D, Chakrabarty A. Lignocaine toxicity after anterior nasal packing. Indian J Anaesth 2011; 55:427.
  39. Day RO, Chalmers DR, Williams KM, Campbell TJ. The death of a healthy volunteer in a human research project: implications for Australian clinical research. Med J Aust 1998; 168:449.
  40. Horáček M, Vymazal T. Lidocaine not so innocent: Cardiotoxicity after topical anaesthesia for bronchoscopy. Indian J Anaesth 2012; 56:95.
  41. Rincon E, Baker RL, Iglesias AJ, Duarte AM. CNS toxicity after topical application of EMLA cream on a toddler with molluscum contagiosum. Pediatr Emerg Care 2000; 16:252.
  42. Maulidi H, McNair C, Seller N, et al. Arrhythmia associated with tetracaine in an extremely low birth weight premature infant. Pediatrics 2012; 130:e1704.
  43. Oni G, Brown S, Burrus C, et al. Effect of 4% topical lidocaine applied to the face on the serum levels of lidocaine and its metabolite, monoethylglycinexylidide. Aesthet Surg J 2010; 30:853.
  44. Sugiyama K, Muteki T. Local anesthetics depress the calcium current of rat sensory neurons in culture. Anesthesiology 1994; 80:1369.
  45. Drachman D, Strichartz G. Potassium channel blockers potentiate impulse inhibition by local anesthetics. Anesthesiology 1991; 75:1051.
  46. Olschewski A, Bräu ME, Olschewski H, et al. ATP-dependent potassium channel in rat cardiomyocytes is blocked by lidocaine. Possible impact on the antiarrhythmic action of lidocaine. Circulation 1996; 93:656.
  47. Wheeler DM, Bradley EL, Woods WT Jr. The electrophysiologic actions of lidocaine and bupivacaine in the isolated, perfused canine heart. Anesthesiology 1988; 68:201.
  48. Valenzuela C, Delpón E, Tamkun MM, et al. Stereoselective block of a human cardiac potassium channel (Kv1.5) by bupivacaine enantiomers. Biophys J 1995; 69:418.
  49. Scott DB, Jebson PJ, Braid DP, et al. Factors affecting plasma levels of lignocaine and prilocaine. Br J Anaesth 1972; 44:1040.
  50. BRAID DP, SCOTT DB. THE SYSTEMIC ABSORPTION OF LOCAL ANALGESIC DRUGS. Br J Anaesth 1965; 37:394.
  51. McNamara PJ, Alcorn J. Protein binding predictions in infants. AAPS PharmSci 2002; 4:E4.
  52. Meunier JF, Goujard E, Dubousset AM, et al. Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with and without biliary atresia. Anesthesiology 2001; 95:87.
  53. Larsson BA, Lönnqvist PA, Olsson GL. Plasma concentrations of bupivacaine in neonates after continuous epidural infusion. Anesth Analg 1997; 84:501.
  54. Veering BT, Burm AG, van Kleef JW, et al. Epidural anesthesia with bupivacaine: effects of age on neural blockade and pharmacokinetics. Anesth Analg 1987; 66:589.
  55. bowdle, AT, Freund, et al. Age-dependent Lidocaine Pharmacokinetics During Lumbar Peridural Anesthesia with Lidocaine Hydrocarbonate or Lidocaine Hydrochloride. Regional Anesthesia 1986; 11:123.
  56. Paqueron X, Boccara G, Bendahou M, et al. Brachial plexus nerve block exhibits prolonged duration in the elderly. Anesthesiology 2002; 97:1245.
  57. Thomson PD, Melmon KL, Richardson JA, et al. Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann Intern Med 1973; 78:499.
  58. Pere P, Salonen M, Jokinen M, et al. Pharmacokinetics of ropivacaine in uremic and nonuremic patients after axillary brachial plexus block. Anesth Analg 2003; 96:563.
  59. Jokinen MJ, Neuvonen PJ, Lindgren L, et al. Pharmacokinetics of ropivacaine in patients with chronic end-stage liver disease. Anesthesiology 2007; 106:43.
  60. Butterworth JF 4th, Walker FO, Lysak SZ. Pregnancy increases median nerve susceptibility to lidocaine. Anesthesiology 1990; 72:962.
  61. Moller RA, Datta S, Fox J, et al. Effects of progesterone on the cardiac electrophysiologic action of bupivacaine and lidocaine. Anesthesiology 1992; 76:604.
  62. Tsen LC, Tarshis J, Denson DD, et al. Measurements of maternal protein binding of bupivacaine throughout pregnancy. Anesth Analg 1999; 89:965.
  63. Rosen MA, Thigpen JW, Shnider SM, et al. Bupivacaine-induced cardiotoxicity in hypoxic and acidotic sheep. Anesth Analg 1985; 64:1089.
  64. Wong GK, Joo DT, McDonnell C. Lipid resuscitation in a carnitine deficient child following intravascular migration of an epidural catheter. Anaesthesia 2010; 65:192.
  65. Weinberg GL, Laurito CE, Geldner P, et al. Malignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy. J Clin Anesth 1997; 9:668.
  66. Wong GK, Crawford MW. Carnitine deficiency increases susceptibility to bupivacaine-induced cardiotoxicity in rats. Anesthesiology 2011; 114:1417.
  67. Rahiri J, Tuhoe J, Svirskis D, et al. Systematic review of the systemic concentrations of local anaesthetic after transversus abdominis plane block and rectus sheath block. Br J Anaesth 2017; 118:517.
  68. Griffiths JD, Barron FA, Grant S, et al. Plasma ropivacaine concentrations after ultrasound-guided transversus abdominis plane block. Br J Anaesth 2010; 105:853.
  69. Kato N, Fujiwara Y, Harato M, et al. Serum concentration of lidocaine after transversus abdominis plane block. J Anesth 2009; 23:298.
  70. Sakai T, Manabe W, Kamitani T, et al. [Ropivacaine-induced late-onset systemic toxicity after transversus abdominis plane block under general anesthesia: successful reversal with 20% lipid emulsion]. Masui 2010; 59:1502.
  71. Landy C, Gagnon N, Boulland P, et al. Seizures associated with local anaesthetic intoxication. Br J Anaesth 2012; 109:463.
  72. Griffiths JD, Le NV, Grant S, et al. Symptomatic local anaesthetic toxicity and plasma ropivacaine concentrations after transversus abdominis plane block for Caesarean section. Br J Anaesth 2013; 110:996.
  73. Weiss E, Jolly C, Dumoulin JL, et al. Convulsions in 2 patients after bilateral ultrasound-guided transversus abdominis plane blocks for cesarean analgesia. Reg Anesth Pain Med 2014; 39:248.
  74. Mulroy MF, Weller RS, Liguori GA. A checklist for performing regional nerve blocks. Reg Anesth Pain Med 2014; 39:195.
  75. Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med 2004; 29:564.
  76. Corvetto MA, Echevarría GC, De La Fuente N, et al. Comparison of plasma concentrations of levobupivacaine with and without epinephrine for transversus abdominis plane block. Reg Anesth Pain Med 2012; 37:633.
  77. Karmakar MK, Ho AM, Law BK, et al. Arterial and venous pharmacokinetics of ropivacaine with and without epinephrine after thoracic paravertebral block. Anesthesiology 2005; 103:704.
  78. Leighton BL, Topkis WG, Gross JB, et al. Multiport epidural catheters: does the air test work? Anesthesiology 2000; 92:1617.
  79. Norris MC, Ferrenbach D, Dalman H, et al. Does epinephrine improve the diagnostic accuracy of aspiration during labor epidural analgesia? Anesth Analg 1999; 88:1073.
  80. Norris MC, Fogel ST, Dalman H, et al. Labor epidural analgesia without an intravascular "test dose". Anesthesiology 1998; 88:1495.
  81. Guay J. The epidural test dose: a review. Anesth Analg 2006; 102:921.
  82. Polaner DM, Zuk J, Luong K, Pan Z. Positive intravascular test dose criteria in children during total intravenous anesthesia with propofol and remifentanil are different than during inhaled anesthesia. Anesth Analg 2010; 110:41.
  83. Takahashi S, Tanaka M. Reduced efficacy of simulated epidural test doses in sevoflurane-anesthetized adults. Can J Anaesth 1999; 46:433.
  84. Tanaka M, Takahashi S, Kondo T, Matsumiya N. Efficacy of simulated epidural test doses in adult patients anesthetized with isoflurane: a dose-response study. Anesth Analg 1995; 81:987.
  85. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg 2012; 115:1353.
  86. Ecoffey C, Lacroix F, Giaufré E, et al. Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF). Paediatr Anaesth 2010; 20:1061.
  87. Llewellyn N, Moriarty A. The national pediatric epidural audit. Paediatr Anaesth 2007; 17:520.
  88. Abrahams MS, Aziz MF, Fu RF, Horn JL. Ultrasound guidance compared with electrical neurostimulation for peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials. Br J Anaesth 2009; 102:408.
  89. Neal JM. Ultrasound-guided regional anesthesia and patient safety: An evidence-based analysis. Reg Anesth Pain Med 2010; 35:S59.
  90. Eren G, Altun E, Pektas Y, et al. To what extent can local anesthetics be reduced for infraclavicular block with ultrasound guidance? Anaesthesist 2014; 63:760.
  91. O'Donnell BD, Iohom G. Local anesthetic dose and volume used in ultrasound-guided peripheral nerve blockade. Int Anesthesiol Clin 2010; 48:45.
  92. Luo M, Yun X, Chen C, et al. Giving Priority to Lipid Administration Can Reduce Lung Injury Caused by Epinephrine in Bupivacaine-Induced Cardiac Depression. Reg Anesth Pain Med 2016; 41:469.
  93. Weinberg GL, Di Gregorio G, Ripper R, et al. Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose. Anesthesiology 2008; 108:907.
  94. Di Gregorio G, Schwartz D, Ripper R, et al. Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-induced cardiac arrest. Crit Care Med 2009; 37:993.
  95. Cave G, Harrop-Griffiths W, Harvey M, et al. Management of Severe Local Anaesthetic Toxicity. AAGBI Safety Guideline 2010.
  96. Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest. Anesth Analg 2009; 108:1344.
  97. Hoegberg LC, Bania TC, Lavergne V, et al. Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. Clin Toxicol (Phila) 2016; 54:167.
  98. Cave G, Harvey M, Graudins A. Intravenous lipid emulsion as antidote: a summary of published human experience. Emerg Med Australas 2011; 23:123.
  99. Cave G, Harvey M, Willers J, et al. LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry. J Med Toxicol 2014; 10:133.
  100. Weinberg GL. Lipid emulsion infusion: resuscitation for local anesthetic and other drug overdose. Anesthesiology 2012; 117:180.
  101. Wagner M, Zausig YA, Ruf S, et al. Lipid rescue reverses the bupivacaine-induced block of the fast Na+ current (INa) in cardiomyocytes of the rat left ventricle. Anesthesiology 2014; 120:724.
  102. Partownavid P, Umar S, Li J, et al. Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats. Crit Care Med 2012; 40:2431.
  103. Rahman S, Li J, Bopassa JC, et al. Phosphorylation of GSK-3β mediates intralipid-induced cardioprotection against ischemia/reperfusion injury. Anesthesiology 2011; 115:242.
  104. Litonius E, Tarkkila P, Neuvonen PJ, Rosenberg PH. Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans. Anaesthesia 2012; 67:600.
  105. Dureau P, Charbit B, Nicolas N, et al. Effect of Intralipid® on the Dose of Ropivacaine or Levobupivacaine Tolerated by Volunteers: A Clinical and Pharmacokinetic Study. Anesthesiology 2016; 125:474.
  106. Heinonen JA, Litonius E, Salmi T, et al. Intravenous lipid emulsion given to volunteers does not affect symptoms of lidocaine brain toxicity. Basic Clin Pharmacol Toxicol 2015; 116:378.
  107. Shi K, Xia Y, Wang Q, et al. The effect of lipid emulsion on pharmacokinetics and tissue distribution of bupivacaine in rats. Anesth Analg 2013; 116:804.
  108. Fettiplace MR, Lis K, Ripper R, et al. Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. J Control Release 2015; 198:62.
  109. Neal JM, Bernards CM, Butterworth JF 4th, et al. ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med 2010; 35:152.
  110. https://eccguidelines.heart.org/wp-content/themes/eccstaging/dompdf-master/pdffiles/part-10-special-circumstances-of-resuscitation.pdf.
  111. AAGBI Safety Guideline: Management of Severe Local Anesthetic Toxicity. https://www.aagbi.org/sites/default/files/la_toxicity_2010_0.pdf (Accessed on April 04, 2016).
  112. Ruan W, French D, Wong A, et al. A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro more effectively than a long-chain emulsion. Anesthesiology 2012; 116:334.
  113. Fettiplace MR, Ripper R, Lis K, et al. Rapid cardiotonic effects of lipid emulsion infusion*. Crit Care Med 2013; 41:e156.
  114. Sampson CS, Bedy SM. Lipid emulsion therapy given intraosseously in massive verapamil overdose. Am J Emerg Med 2015; 33:1844.e1.
  115. https://eccguidelines.heart.org/index.php/circulation/cpr-ecc-guidelines-2/part-10-special-circumstances-of-resuscitation/?strue=1&id=5.
  116. http://www.acmt.net/resources_position.html.
  117. Levine M, Skolnik AB, Ruha AM, et al. Complications following antidotal use of intravenous lipid emulsion therapy. J Med Toxicol 2014; 10:10.
  118. Grunbaum AM, Gilfix BM, Gosselin S, Blank DW. Analytical interferences resulting from intravenous lipid emulsion. Clin Toxicol (Phila) 2012; 50:812.
  119. Grunbaum AM, Gilfix BM, Hoffman RS, et al. Review of the effect of intravenous lipid emulsion on laboratory analyses. Clin Toxicol (Phila) 2016; 54:92.
  120. Schwarz ES, Arroyo-Plasencia AM, Mullins ME. Other complications following lipid emulsion therapy : Re: Levine M, Skolnik AB, Ruha AM, et al. (2013) Complications following antidotal use of intravenous lipid emulsion therapy. J Med Toxicol Dec 13. [Epub ahead of print]. J Med Toxicol 2014; 10:247.
  121. Rodríguez B, Wilhelm A, Kokko KE. Lipid emulsion use precluding renal replacement therapy. J Emerg Med 2014; 47:635.
  122. Jeong J. Continuous renal replacement therapy circuit failure after antidote administration. Clin Toxicol (Phila) 2014; 52:1296.
  123. Lee HM, Archer JR, Dargan PI, Wood DM. What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient? Clin Toxicol (Phila) 2015; 53:145.
  124. Muller SH, Diaz JH, Kaye AD. Intralipid Emulsion Rescue Therapy: Emerging Therapeutic Indications in Medical Practice. J La State Med Soc 2016; 168:101.
  125. Jakkala-Saibaba R, Morgan PG, Morton GL. Treatment of cocaine overdose with lipid emulsion. Anaesthesia 2011; 66:1168.